Insulin-like growth factor binding protein 4-1 (IGFBP4-1), a new long noncoding RNA (lncRNA), has been reported to contribute to tumorigenesis and has been suggested to be a poor prognostic marker in human lung cancer. However, there still lacks basic studies that investigated the biological role of IGFBP4-1 in bladder urothelial carcinoma to date. In this study, we investigated the relationship between IGFBP4-1 expression and prognosis in patients with bladder cancer. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGFBP4-1 function by up-regulating or down-regulating IGFBP4-1 in bladder cancer cells. A xenograft mice model was used to validate the in vitro results. Blockade of Janus kinase-signal transducer and activator of transcription pathway (JAK/STAT) was used to evaluate JAK/STAT signaling activity. The results showed that IGFBP4-1 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its expression level was positively correlated with poor prognosis in bladder cancer patients. Overexpression of IGFBP4-1 markedly promoted cell proliferation and cell cycle progression, and inhibited cell apoptosis, while knockdown of IGFBP4-1 notably suppressed the proliferation, promoted cell apoptosis, and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGFBP4-1 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumor-promoting activity of IGFBP4-1. Tumor growth in vivo was also suppressed by knocking down of IGFBP4-1. In conclusion, IGFBP4-1 promoted bladder cancer progression by activating the JAK/STAT signaling pathway. These findings suggest that IGFBP4-1 exhibits an oncogenic role in the development of human bladder cancer.
Keywords: IGFBP4-1; JAK/STAT; bladder cancer; prognosis; proliferation.
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